A Philippon

Pierre and Marie Curie University - Paris 6, Lutetia Parisorum, Île-de-France, France

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Publications (166)414.81 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Lactobacillus urinary tract infection (UTI) seems exceptionally reported. Nevertheless, with the introduction of a chromogenic medium UriSelect 4, eight cases of UTI in old women (mean of 81.2 years) mediated by Lactobacillus delbrueckii identified by DNA sequencing were reported between 2007 and 2009.
    Pathologie Biologie 06/2010; 60(2):140-2. · 1.67 Impact Factor
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    ABSTRACT: We studied the genetic organization of bla(ACC-1) in 14 isolates of Enterobacteriaceae from France, Tunisia, and Germany. In a common ancestor, ISEcp1 was likely involved in the mobilization of this gene from the Hafnia alvei chromosome to a plasmid. Other genetic events involving insertion sequences (particularly IS26), transposons (particularly Tn1696), or sulI-type integrons have occurred, leading to complex genetic environments.
    Antimicrobial Agents and Chemotherapy 01/2007; 50(12):4177-81. · 4.57 Impact Factor
  • FEMS Microbiology Letters 03/2006; 8(4):191 - 194. · 2.05 Impact Factor
  • A Philippon, G Arlet
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    ABSTRACT: The acquired resistance against the wide-spectrum and highly stable beta-lactams including third-generation cephalosporins (3GC) and carbapenems is constinuously increasing and widespead with the discovery of various plasmid-encoded, or genes cassette or integrons coding for a novel beta-lactamase, always a major mechanism of resistance. To explain resistance against 3GC, with the continuing story with TEM and SHV mutated enzymes, several types of ESBL (class A) emerge the CTX-M type, at least CTX-M-40, but also other non predominant types intitled BES, GES, PLA, PER, VEB. The wider resistance including 3GC, cephamycins and beta-lactamase inhibitor is correlated to synthesis of transferable cephalosporinases (class C) usually located in the chromosome but mobilized from Enterobacter spp., Citrobacter freundii, Hafnia alvei, Morganella morganii, Aeromonas caviae. Such genes encoded the following types: ACC-1, ACT-1, CFE-1, CMY group, DHA-1, FOX group, MIR-1, MOX-1. Finally the resistance against carbapemens e.g. imipenem originally restricted to Pseudomonas aeruginosa, then to Acinetobacter baumannii and finally to enterobacteria is related to production of novel enzymes (classes B, D and A) denominated IMP, VIM SME, GIM, OXA, KPC. A striking exemple of evolution towards more and more resistance is given by Salmonella, even from animal origins, a great threat fo public health. So far it appears necessary to perform molecular approaches to identify such enzymatic production. Finally because the absence of real new drugs, the discovery of some progenitors of the gene beta-lactamase, a strict control of beta-lactam antibiotics must be provide not only in medecine or veterinary field but also in agriculture, including aquaculture for example.
    Annales de biologie clinique 01/2006; 64(1):37-51. · 0.30 Impact Factor
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    ABSTRACT: The chromosomally encoded class C -lactamases confer a natural resistance to -lactams, which is typical of a number of gram-negative species. Since the 1980s, plasmid-encoded AmpC-type -lactamases have been found worldwide, most often in organisms lacking inducible chromosomal AmpC enzymes (13). Plasmid-carried ampC genes originate from the chromosomal ampC genes of organisms such as Citro- bacter freundii (CMY type), Enterobacter spp. (MIR-1 and ACT-1), Morganella morganii (DHA type), and Hafnia alvei (ACC-1) (13). ACC-1 was characterized in isolates of several species, such as Klebsiella pneumoniae, Proteus mirabilis, Salmonella enterica, and Escherichia coli, from Germany, France, Tunisia, Spain, and The Netherlands (2, 3, 6-9, 11, 12, 15). In France, noso- comial outbreaks following the admission of a patient trans- ferred from Tunisia, a country which seems to be a potential reservoir, were described (11, 12). The ACC-1-producing rifampin-resistant K. pneumoniae SLK54 strain, isolated in Saint-Louis Hospital in Paris, France, was previously studied by cloning experiments, and the genetic organizations of both plasmid-mediated genes, blaACC-1 and arr-2, were established (1, 11). The presence of IS26 in both recombinant plasmids suggests that arr-2 and blaACC-1 could be linked in the K. pneumoniae SLK54 plasmid. In this study, we have tested this hypothesis, and we have analyzed the genetic environment of the blaACC-1 gene in a collection of ACC-1- producing isolates, including 11 K. pneumoniae, one P. mira- bilis, and two S. enterica isolates from different settings. Table 1 lists the 14 clinical isolates and their sources. Most
    Antimicrobial Agents and Chemotherapy - ANTIMICROB AGENTS CHEMOTHER. 01/2006; 50(12):4177-4181.
  • A. Philippon, G. Arlet
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    ABSTRACT: Among gram-negative bacteria, the role of β-lactamases for natural and acquired resistance is essential and more and more complex. Numerous corresponding genes located in chromosome, plasmid, integron or CR (common region) were cloned and sequenced showing a very high diversity among this type of inactivating enzymes. A lot of genetic answers were developed by bacteria after introduction of new drugs such as β-lactam antibiotics. Such adaptability of bacterial world must lead to limit the abuse of prescriptions and a better use of drugs.
    Antibiotiques 01/2005; 7(4):247-259.
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    ABSTRACT: We analyzed 19 clinical isolates of the family Enterobacteriaceae (16 Escherichia coli isolates and 3 Klebsiella pneumoniae isolates) collected from four different hospitals in Paris, France, from 2000 to 2002. These strains had a particular extended-spectrum cephalosporin resistance profile characterized by a higher level of resistance to cefotaxime and aztreonam than to ceftazidime. The bla(CTX-M) genes encoding these beta-lactamases were involved in this resistance, with a predominance of bla(CTX-M-15). Ten of the 19 isolates produced both TEM-1- and CTX-M-type enzymes. One strain (E. coli TN13) expressed CMY-2, TEM-1, and CTX-M-14. bla(CTX-M) genes were found on large plasmids. In 15 cases the same insertion sequence, ISEcp1, was located upstream of the 5' end of the bla(CTX-M) gene. In one case we identified an insertion sequence designated IS26. Examination of the other three bla(CTX-M) genes by cloning, sequencing, and PCR analysis revealed the presence of a complex sul1-type integron that includes open reading frame ORF513, which carries the bla gene and the surrounding DNA. Five isolates had the same plasmid DNA fingerprint, suggesting clonal dissemination of CTX-M-15-producing strains in the Paris area.
    Antimicrobial Agents and Chemotherapy 05/2004; 48(4):1249-55. · 4.57 Impact Factor
  • L. Prots, A. Philippon
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    ABSTRACT: Résumé Depuis plus d’une décennie, le séquençage de certains gènes bactériens est considéré comme la méthode la plus performante et la plus rapide des études taxonomiques avec la reconsidération des grands groupes et genres bactériens. L’autre critère génétique de la taxonomie est celui de l’hybridation entre ADN.
    Bio Tribune Magazine 01/2003; 8(1):30-33.
  • G. Arlet, A. Philippon
    Revue Française des Laboratoires 01/2003; 2003(352).
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    ABSTRACT: Because a multiresistant K. pneumoniae outbreak detected in an intensive care unit of a parisian hospital, combined to the production of the plasmid-encoded cephalosporinase ACC-1, a probable importation via a patient was suggested from another country (Tunisia). The investigation was conducted to examine 35 clinical strains of enterobacteria resistant to ceftazidime without synergy towards Augmentin. Other test of synergy with two inhibitors, BRL 42715, Ro 48-5545 was performed by diffusion method and deposit of 10 micrograms of inhibitor on disks containing ceftazidime, cefoxitin and cefotetan. Synergies were obtained suggesting a probable production of ACC-1 type among six isolates of K. pneumoniae (two), Proteus mirabilis (one) and Salmonella (three) issued from different units. The isoelectric focusing on gel revealed at least one band of beta-lactamase activity at 7.8 but also demonstrated the simultaneous production of several probable beta-lactamases including TEM-type, SHV-2 and ACC-1 among S. enterica ser. Livingstone. The PCR of the gene blaacc-1 was positive. The sequencing (1160 pb) of two products showed high identity (99-100%) with the gene blaacc-1 deposited in 1999. Finally the ACC-1 type reported in Tunisia was probably imported in France via a patient. Because a simultaneous synthesis of ESBL and ACC-1 type, its presence may be invisible and need more investigation.
    Pathologie Biologie 03/2002; 50(1):7-11. · 1.67 Impact Factor
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    ABSTRACT: Because a multiresistant K. pneumoniae outbreak detected in an intensive care unit of a parisian hospital, combined to the production of the plasmid-encoded cephalosporinase ACC-1, a probable importation via a patient was suggested from another country (Tunisia). The investigation was conducted to examine 35 clinical strains of enterobacteria resistant to ceftazidime without synergy towards Augmentin®. Other test of synergy with two inhibitors, BRL 42715, Ro 48-5545 was performed by diffusion method and deposit of 10 μg of inhibitor on disks containing ceftazidime, cefoxitin and cefotetan. Synergies were obtained suggesting a probable production of ACC-1 type among six isolates of K. pneumoniae (two), Proteus mirabilis (one) and Salmonella (three) issued from different units. The isoelectric focusing on gel revealed at least one band of β-lactamase activity at 7.8 but also demonstrated the simultaneous production of several probable β-lactamases including TEM-type, SHV-2 and ACC-1 among S. enterica ser. Livingstone. The PCR of the gene blaacc-1 was positive. The sequencing (1160 pb) of two products showed high identity (99–100%) with the gene blaacc-1 deposited in 1999. Finally the ACC-1 type reported in Tunisia was probably imported in France via a patient. Because a simultaneous synthesis of ESBL and ACC-1 type, its presence may be invisible and need more investigation.
    Pathologie Biologie - PATHOL BIOL. 01/2002; 50(1):7-11.
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    Antimicrobial Agents and Chemotherapy 11/2001; 45(10):2971-2. · 4.57 Impact Factor
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    ABSTRACT: A multicenter study was carried out to evaluate the performance of a new commercial automated system in comparison with that of the reference agar dilution method. Ten clinical microbiology laboratories tested a collection of 61 strains of gram-negative bacilli (49 Enterobacteriaceae and 12 Pseudomonas aeruginosa), and 6 other laboratories tested a collection of 55 strains of gram-positive cocci (10 enterococci and 45 staphylococci) against 10-20 antimicrobial agents. The strains were selected on the basis that they harbored challenging and characterized mechanisms of resistance. In comparison with the agar reference method, the automated system gave an overall essential agreement (+/-1 dilution) of 94.5%, 93.5%, and 97% for the gram-negative bacilli, enterococci, and staphylococci, respectively. According to the interpretive standards of the National Committee for Clinical Laboratory Standards, the category agreement ranged from 96 to 96.4% for the three sets of organisms. The accuracy of the automated system, as determined by the kappa test, ranged from 0.80 to 0.88, reflecting an almost perfect agreement with the reference technique. Very major, major, and minor errors obtained with the automated system were 0.3%, 2.9%, and 6.6% for gram-negative bacilli, 3.4%, 0%, and 5% for enterococci, and 1%, 1.6%, and 2.7% for staphylococci, respectively. The high rate of very major errors in enterococci was mostly due to a single strain of multidrug-resistant Enterococcus faecium, which was found susceptible to several antibiotics in a majority of participant laboratories. The use of a heavy inoculum and of a broth test medium by the automated system might account for a better expression of certain resistance mechanisms, including beta-lactamases, as compared to the agar dilution reference method. The interlaboratory reproducibility was acceptable, as shown by the narrow dispersion of MICs and by the results of quality control.
    European Journal of Clinical Microbiology 10/2001; 20(9):626-35. · 3.02 Impact Factor
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    ABSTRACT: Ochrobactrum anthropi, formerly known as CDC group Vd, is an oxidase-producing, gram-negative, obligately aerobic, non-lactose-fermenting bacillus of low virulence that occasionally causes human infections. It is highly resistant to all beta-lactams except imipenem. A clinical isolate, SLO74, and six reference strains were tested. MICs of penicillins, aztreonam, and most cephalosporins tested, including cefotaxime and ceftazidime, were >128 microg/ml and of cefepime were 64 to >128 microg/ml. Clavulanic acid was ineffective and tazobactam had a weak effect in association with piperacillin. Two genes, ampR and ampC, were cloned by inserting restriction fragments of genomic DNA from the clinical strain O. anthropi SLO74 into pBK-CMV to give the recombinant plasmid pBK-OA1. The pattern of resistance to beta-lactams of this clone was similar to that of the parental strain, except for its resistance to cefepime (MIC, 0.5 ,micro/ml). The deduced amino acid sequence of the AmpC beta-lactamase (pI, 8.9) was only 41 to 52% identical to the sequence of other chromosomally encoded and plasmid-encoded class C beta-lactamases. The kinetic properties of this beta-lactamase were typical for this class of beta-lactamases. Upstream from the ampC gene, the ampR gene encodes a protein with a sequence that is 46 to 62% identical to those of other AmpR proteins and with an amino-terminal DNA-binding domain typical of transcriptional activators of the Lys-R family. The deduced amino acid sequences of the ampC genes of the six reference strains were 96 to 99% identical to the sequence of the clinical strain. The beta-lactamase characterized from strain SLO74 was named OCH-1 (gene, bla(OCH-I)).
    Antimicrobial Agents and Chemotherapy 09/2001; 45(8):2324-30. · 4.57 Impact Factor
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    ABSTRACT: Enterobacter cloacae CHE, a clinical strain with overproduced cephalosporinase was found to be highly resistant to the new cephalosporins, cefepime and cefpirome (MICs> or =128 microg ml(-1)). The strain was isolated from a child previously treated with cefepime. The catalytic efficiency of the purified enzyme with the third-generation cephalosporins, cefepime and cefpirome, was 10 times higher than that with the E. cloacae P99 enzyme. This was mostly due to a decrease in K(m) for these beta-lactams. The clinical isolate produced large amounts of the cephalosporinase because introduction of the ampD gene decreased ampC expression and partially restored the wild-type phenotype. Indeed, MICs of cefepime and cefpirome remained 10 times higher than those for a stable derepressed clinical isolate (OUDhyp) transformed with an ampD gene. Sequencing of the ampC gene showed that 18 nucleotides had been deleted, corresponding to the six amino acids SKVALA (residues 289--294). According to the crystal structure of P99 beta-lactamase, this deletion was located in the H-10 helix. The ampR-ampC genes from the clinical isolates CHE and OUDhyp were cloned and expressed in Escherichia coli JM101. The MICs of cefpirome and cefepime of E. coli harboring ampC and ampR genes from CHE were 100--200 times higher than those of E. coli harboring ampC and ampR genes from OUDhyp. This suggests that the deletion, confirmed by sequencing of the ampC gene, is involved in resistance to cefepime and cefpirome. However, the high level of resistance to cefepime and cefpirome observed in the E. cloacae clinical isolate was due to a combination of hyperproduction of the AmpC beta-lactamase and structural modification of the enzyme. This is the first example of an AmpC variant conferring resistance to cefepime and cefpirome, isolated as a clinical strain.
    FEMS Microbiology Letters 03/2001; 195(2):185-90. · 2.05 Impact Factor
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    Antimicrobial Agents and Chemotherapy - ANTIMICROB AGENTS CHEMOTHER. 01/2001; 45(10):2971-2972.
  • Pathologie Biologie 12/2000; 48(9):832-71. · 1.67 Impact Factor
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    ABSTRACT: Fifty-two strains of Klebsiella pneumoniae producing an AmpC-type plasmid-mediated beta-lactamase were isolated from 13 patients in the same intensive care unit between March 1998 and February 1999. These strains were resistant to ceftazidime, cefotaxime and ceftriaxone, but susceptible to cefoxitin, cefepime and aztreonam. Plasmid content and genomic DNA restriction pattern analysis suggested dissemination of a single clone. Two beta-lactamases were identified, TEM-1 and ACC-1. We used internal bla(ACC-1) primers, to sequence PCR products obtained from two unrelated strains of Hafnia alvei. Our results show that the ACC-1 beta-lactamase was derived from the chromosome-encoded AmpC-type enzyme of H. alvei.
    FEMS Microbiology Letters 07/2000; 187(1):35-40. · 2.05 Impact Factor
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    ABSTRACT: A plasmid-encoded extended-spectrum TEM beta-lactamase with a pI of 5.5 was detected in a Capnocytophaga ochracea clinical isolate. The bla gene was associated with a strong TEM-2 promoter and was derived from bla(TEM-1a) with a single-amino-acid substitution: Glu(104)-->Lys, previously assigned to TEM-17, which is thus the first TEM beta-lactamase to be reported in the phylum Flavobacter-Bacteroides.
    Antimicrobial Agents and Chemotherapy 04/2000; 44(3):760-2. · 4.57 Impact Factor
  • Médecine et Maladies Infectieuses 01/2000; 30(1). · 0.75 Impact Factor

Publication Stats

4k Citations
414.81 Total Impact Points

Institutions

  • 2007
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 1997
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • King Fahd Military Medical Complex
      Az̧ Z̧ahrān, Eastern Province, Saudi Arabia
  • 1996
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
    • Università degli Studi di Genova
      Genova, Liguria, Italy
  • 1995
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1989–1991
    • Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Île-de-France, France
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Henri Mondor (Hôpitaux Universitaires Henri Mondor)
      • Service de Bactériologie - Virologie
      Créteil, Ile-de-France, France
  • 1990
    • Hôpital Charles-Nicolle
      Tunis-Ville, Tūnis, Tunisia
  • 1984
    • Université René Descartes - Paris 5
      • Faculty of medicine
      Lutetia Parisorum, Île-de-France, France